Published byStanford Medicine

Skin is superficial, literally. But it’s also really deep, as I realized while editing the just-published issue of Stanford Medicine magazine. The summer issue features the special report “Skin deep: The science of the body’s surface.”

I learned from the chair of Stanford’s Department of Dermatology, Paul Khavari, MD, PhD, that thousands of diseases affect the skin. And I learned it’s surprisingly abundant: An average-sized adult is covered with about 20 square feet of skin.

Research on skin is thriving, in part, because skin is so easy to get hold of, Khavari told me. “The accessibility of skin tissue to the application of new technologies, including genomics, proteomics, and metabolomics, make this a watershed moment for progress in alleviating the tremendous suffering caused by the global burden of skin disease,” he said.

The magazine, produced with support from the dermatology department, includes articles not only about new treatments, but also insights into how skin works when it’s healthy and how to keep it that way. In a Q&A and audio interview, actress and playwright Anna Deavere Smith, who is African-American, addresses skin’s social meaning, discussing her relationship to her own skin and how, as a writer and actor, she gets under the skin of her characters. The online version of the magazine includes audio of an interview with Smith.

Also in the issue:

“The butterfly effect“: A story about two young men coping with one of the world’s most painful diseases — the skin-blistering condition epidermolysis bullosa — including news about an experimental treatment to replace their broken genes. The online version includes a video with a patient at home and interviews with experts on the condition.

“Surviving melanoma“: A report on progress being made after years of stagnation in treating the most deadly skin cancer: melanoma.

“The rarest of rashes“: A look at one of Stanford Medicine’s great accomplishments in dermatology: successful treatment of a rare but dangerous rash — cutaneous lymphoma, a form of blood cancer that spreads to the skin.

“Wither youth“: A feature on research seeking to answer the question: Why does skin age?

“New lungs, new life“: The story of a young woman who lost her smile and had it restored through surgery.

The issue also includes a story considering the rise in number of castoff donor hearts, despite a shortage of the organs for transplants, and an excerpt from Jonas Salk: A Life, a new biography of the polio-vaccine pioneer, written by retired Stanford professor Charlotte Jacobs, MD.

Asking patients how they would like to die is not a question that comes easy to most doctors. Not surprisingly, most of us – doctors and patients alike – prefer to avoid the topic completely. That’s not good, says VJ Periyakoil, MD, director of palliative care education and training at Stanford.

As I wrote in an Inside Stanford Medicinearticle on Periyakoil’s new study on end-of-life conversations:

End-of-life conversations help clarify for doctors what matters most to patients in their waning days of life… “What are their hopes, wants, needs and fears? Do they want to die at the hospital on a machine? Do they want to die at home? We can’t know unless we have a conversation,” she said.

Her study, published today in PLOS One, surveyed more than 1,000 medical residents and found that most balk at talking with seriously ill patients about what’s important to them in their final days, especially if the patient’s ethnicity is different than their own. Of those surveyed, 99.99 percent reported barriers, with 86 percent rating them as very challenging.

The upshot for Periyakoil, as she explains in a New York Times column published today, is that if we want to have a say in how we die, we should start that conversation ourselves.

To get these conversations started far and wide, she has launched the Stanford Letter Project – a campaign to empower all adults to take the initiative to talk to their doctor about what matters most to them at life’s end. The project’s website hosts templates for a letter about this to your doctor to get the conversation rolling. The templates are in Mandarin, Spanish and Tagalog as well as English – and Periyakoil says translations in additional languages will be available soon.

How are drugs born? If you’re really curious about this, you’d be fascinated by the weekly meetings of industry experts and academic researchers taking part in Stanford’s drug-development training program known as SPARK.

In his recent review of the book for Nature Chemical Biology, industrial medicinal chemist Derek Lowe, PhD, writes:

I would actually welcome it if this book’s intended audience were broadened even more. Younger scientists starting out in the drug industry would benefit from reading it and getting some early exposure to parts of the process that they’ll eventually have to understand. Journalists covering the industry (especially the small startup companies) will find this book a good reality check for many an over-hopeful press release. Even advanced investors who might want to know what really happens in the labs will find information here that might otherwise be difficult to track down in such a concentrated form.

Lowe also wrote about the book last week on his blog, In the Pipeline, where an interesting discussion has begun.

Neurosurgeon and writer Paul Kalanithi, MD, passed away on Monday. A death is almost always sad, but for me this one is indescribably so – though if he were alive he might convince me of a positive angle.

Kalanithi died at 37 of lung cancer less than a year after finishing his neurosurgery residency at Stanford. During the roughly two years between his diagnosis and death, he spent time as a surgeon saving lives and passing his skills and insights to neurosurgery trainees. But I came to meet him through my work as editor of Stanford Medicine magazine, which published an essay he crafted. His words changed how I think about my life – and, based on the many letters and emails I’ve received, changed how many people looked at theirs as well.

After his diagnosis he wrote essays for The New York Times and Stanford Medicine about his changing perception of mortality and time and the joy he continued to find in life. I interviewed him for a video produced for our magazine, talking with him at his apartment and meeting his wife and baby girl. My colleagues also got to know him by working on stories about his life and illness; just a few days ago, Paul Costello shared on Scope a 45-minute conversation the two had last fall.

Kalanithi’s message, to appreciate every moment, sounds corny when I write it, but in his eloquent words it hits home. In the obituary I wrote today, I shared this excerpt from his Stanford Medicine essay – words he wrote for his infant daughter:

When you come to one of the many moments in life when you must give an account of yourself, provide a ledger of what you have been, and done, and meant to the world, do not, I pray, discount that you filled a dying man’s days with a sated joy, a joy unknown to me in all my prior years, a joy that does not hunger for more and more, but rests, satisfied. In this time, right now, that is an enormous thing.

Why is it that giant tortoises typically live for 100 years but humans in the United States are lucky to make it past 80? And why does the life of an African killifish zip past in a matter of months?

I’ve often mused about the variability of life spans and I figure pretty much everyone else has too. But while editing the new issue of Stanford Medicine magazine’s special report on time and health, “Life time: The long and short of it,” I learned that serious scientists believe the limits are not set in stone.

“Ways of prolonging human life span are now within the realm of possibility,” says professor of genetics Anne Brunet, PhD, in “The Time of Your Life,” an article on the science of life spans. My first thought was, wow! Then I wondered if some day humans could live like the “immortal jellyfish,” which reverts back to its polyp state, matures and reverts again, ad infinitum. Now that would be interesting.

Also covered in the issue:

“Hacking the Biological Clock”: An article on attempts to co-opt the body’s timekeepers to treat cancer, ease jetlag and reverse learning disabilities.

“Time Lines”: A Q&A with bestselling author and physician Abraham Verghese, MD, on the timeless rituals of medicine. (The digital edition includes audio of an interview with Verghese.)

“Tick Tock”: A blow-by-blow account of the air-ambulance rescue of an injured toddler.

“Before I Go”: An essay about the nature of time from a young neurosurgeon who is now living with an advanced form of lung cancer. (The neurosurgeon, Paul Kalanithi, MD, is featured in the video above, and our digital edition also includes audio of an interview with him.)

The issue also includes a story about the danger-fraught birth of an unusual set of triplets and an excerpt from the new biography of Nobel Prize-winning Stanford biochemist Paul Berg, PhD, describing the sticky situation he found himself in graduate school.

This year’s most-read Stanford Medicine magazine stories were all about the heart, surgery and the immune system – the themes of this year’s three issues. The top 10 (as determined by pageviews on our website):

If you want to understand the human immune system, try studying humans – not mice. That’s what Mark Davis, PhD, urges in a special report on the immune system in the new issue of Stanford Medicine magazine.

“Inbred mice have not, in most cases, been a reliable guide for developing treatments for human immunological diseases,” Davis says in the special report, titled “Balancing act: The immune system.”

As the editor of the magazine, I wanted to feature a story that showed how human-focused immunology research plays out. So I was glad to learn that the center is in the midst of its largest study so far – one to figure out the cause of chronic fatigue syndrome. A team led by Stanford professor of infectious diseases José Montoya, MD, is looking for meaningful patterns in the components of blood samples gathered from 200 patients with chronic fatigue syndrome and 400 healthy subjects.

“It’s like dumping a hundred different puzzles on the floor and trying to find two pieces that fit,” Davis says in our story. We also have a video about a patient’s seven-year battle with chronic fatigue, from despair to recovery.

“My rendezvous with insanity”: a Q&A with Susannah Cahalan, author of Brain on Fire: My Month of Madness, her memoir of surviving an autoimmune attack on her brain

“The swashbuckler”: on look back to the early days of molecular biology when Mark Davis cracked one of the greatest mysteries of the immune system

The issue also includes an article on efforts at the VA Palo Alto Health Care System to use peer-support services to help veterans with post-traumatic stress disorder, and a story on the growing concern that biomedical research results are often erroneous and efforts being made to solve the problem.

It used to be “big hole, big surgeon” — but no more, according to Stanford’s chair of surgery, Tom Krummel, MD, who’s one of the surgeons featured in Stanford Medicine magazine’s report on surgery and life in the operating room, “Inside job: Surgeons at work.”

During his career of more than 30 years, Krummel has seen a massive shift from open surgeries to minimally invasive procedures — major surgeries conducted with tools that work through small openings.

“We do the same big operation. We just don’t make a big hole,” he said in the article leading off the report.

In the same issue, CNN’s chief medical correspondent, neurosurgeon Sanjay Gupta, MD, talks about why he’s “doubling down” on his support for medical marijuana.

As the editor, I’m biased — but I think it’s worth a read, along with the rest of the issue, which includes:

“Sculpting bones”: on lengthening a young girl’s leg using an external fixator — a device described both as draconian and as the perfect blend of engineering and art (Check out our animation by Lighthaus showing how the device works)

Why aren’t we all drowning in fat? Before talking with Mary Teruel, PhD, this question certainly never occurred to me. (On a personal level, though, I admit I’ve wondered about the opposite!) But after our conversation I saw why it’s such a good question — and how great it is that Teruel has come up with an answer.

Normally your body replaces about 10 percent of your fat cells a year, explained Teruel, a Stanford assistant professor of chemical and systems biology. Little by little, the old ones die, and new ones develop from flat, spindly precursor cells.

Teruel knew, based on her previous experiments, that the switch that triggers the conversion of precursor cells into fat cells is an “on-off” sort, not a dimmer which can be dialed up and down.

Here’s what’s going on in a little more detail: The switch controls the amount of PPAR-gamma in a cell. PPAR-gamma is a nuclear receptor protein that is the master regulator of fat-cell development. In precursor cells, the switch is in the “off-state” and there’s no PPAR-gamma in the cell, but when the cell senses a stimulus that can cause fat cell development, the switch flips to the “on-state” and the cell rapidly makes huge amounts of PPAR-gamma which then turns on hundreds of downstream genes that create a full-fledged fat cell over a period of up to 12 days.

So here’s what was puzzling Teruel: Every human has a large number of precursor cells that all sense the same stimulus, but rather than all converting at once to fat cells (causing us to “drown in fat”) for a given strong stimulus, only a few cells develop into fat cells at any given time, allowing a healthy, constant renewal of our fat tissue. What allows this slow, controlled renewal of fat cells, as well as prevents the unhealthy situation in which all fat cells would turn back into precursors when PPAR-gamma drops below the threshold needed to flip the switch on? If you can manipulate the rate fat cells mature, you could do a lot for obesity.
Experiments she did with postdoctoral researcher Robert Ahrends, PhD, and colleagues, explain, and provide clues about how to control the rate at which fat forms.

The answer, they discovered, has two parts. First of all, they discovered that the master fat-regulator switch has multiple layers of feedback. Teruel, who has a PhD in aeronautical engineering, explains that these multiple layers allow the body to control the rate of fat cell formation much as a pilot would control the pitch of an aircraft. Second, they found that not all precursor cells are alike — they vary in the quantity they carry of PPAR-gamma and other regulatory proteins.

This realization is a big deal. For one thing, it gives researchers new ideas for treating obesity and diabetes — so far, conditions that resist effective treatment without serious side effects.

“If you can manipulate the rate fat cells mature, you could do a lot for obesity,” she pointed out.

“This might be the heart of how you treat disease,” said Teruel. “We can’t just use one drug for treatment. Disease is more complicated than people think. It would be like trying to control an airplane and only being able to turn the rudder. This might work in a car or boat, but an airplane can move in three-dimensions, and a change in any one dimension affects the other two. Only controlling one dimension is a sure way to crash the plane.”

Teruel’s Stanford website has more info about her research as well as a striking depiction of a fat cell’s development.

They published the results of their studies on Friday in the journal Science (subscription required). They were supported by Stanford University New Faculty Startup Funds, the National Institutes of Health (grant P50GM107615), the German Research Foundation, and the American Heart Association.

This probably won’t grab as many headlines as the news of a smartphone that wakes you up with the sizzle and smell of bacon, but it should!

A team of Stanford scientists is using 3D printing to create inexpensive adapters that make it easy to use a smartphone and an ordinary examination lens to capture high-quality images of the front and back of the eye. And – what seems to me as just as important – providing a nearly effortless way to share those images.

“Think Instagram for the eyes,” said one of the developers, assistant professor of ophthalmology Robert Chang, MD.

This is a big deal because most primary-care doctors have no good way to see into patients’ eyes, and no easy way to share the images. The usual eye-imaging instruments are expensive and hard to use, and even ophthalmologists who have the equipment and know-how find capturing and sharing the images slow going.

“A picture is truly worth a thousand words… Imagine a car accident victim arriving in the emergency department with an eye injury resulting in a hyphema – blood inside the front of her eye. Normally the physician would have to describe this finding in her electronic record with words alone. Smartphones today not only have the camera resolution to supplement those words with a high-resolution photo, but also the data-transfer capability to upload that photo securely to the medical record in a matter of seconds.”

The scientists describe the adapters, currently dubbed the EyeGo, in two articles in the new issue (volume 3, issue 1) of Journal of Mobile Technology in Medicine. And you can read my story to learn more about the development process, including how Myung pieced together the first prototype (with plastic bits he ordered from the Internet and a few Legos), how mechanical engineering graduate student Alex Jais created the first printed model on his own 3D printer, and how residents Lisa He, MD, and Brian Toy, MD, are leading studies to test them out.

Those interested in using an EyeGo adapter for research or beta-testing can e-mail the team at eyegotech@gmail.com.